Is CRPPA p.Pro5Ser (c.13C>T) pathogenic?

CRPPA p.Pro5Ser (c.13C>T) is classified Uncertain significance in CRPPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-03). AlphaMissense: likely benign (0.0665); Very rare (popmax 0.00156%, afr); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7.

How common is CRPPA p.Pro5Ser (c.13C>T) in the general population?

CRPPA p.Pro5Ser (c.13C>T) is very rare (popmax 0.00156%, afr) (gnomAD).

How is Walker-Warburg syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CRPPA p.Pro5Ser (c.13C>T)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

CRPPA p.Pro5Ser

Q: What condition is associated with CRPPA p.Pro5Ser (c.13C>T)?

CRPPA p.Pro5Ser (c.13C>T) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, autosomal recessive limb-girdle muscular dystrophy type 2U (ClinVar).

c.13C>T · rs1037010291 · VCV540372

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00156%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.19, phastCons 0.004
Regional constraint	o/e 1.14	unconstrained · MANE · 330 kb · p 0.001 · regional, not allelic
Overall
CADD	14.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00156% African / African-American · 1/64,230 alleles

Overall 0.000317% 4/1,260,230 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00431%	23,187
African / African-Americangrpmax	0.00156%	64,230
European (non-Finnish)	0.0001%	998,582

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CRPPA
Protein: p.Pro5Ser
Coding: c.13C>T
MANE Select: NM_001101426
dbSNP: rs1037010291
Type: single nucleotide variant
Location: chr7:16421310 (GRCh38)
Gene constraint: LOEUF 1.462 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.63 · 1 PDB
Residue 5: the 'disordered' region

Full CRPPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2U

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

CRPPA p.Pro5fs Pathogenic ★ same residue
CRPPA c.1120-1G>T Pathogenic ★★ same condition
CRPPA c.258-1G>C Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.835+2T>C Pathogenic/Likely pathogenic ★★ same condition
CRPPA p.Arg184Ter Pathogenic ★★ same condition
CRPPA p.Arg268Ter Pathogenic ★★ same condition
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.1026+5G>C Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/crppa-p-pro5ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown